National Pediatric Cancer Foundation

The National Pediatric Cancer Foundation funds Pediatric cancerresearch with the goal of leading to the treatment and elimination ofpediatric Cancer worldwide.we accomplish our mission through our research initiative, the sunshineproject, an innovative collaboration of 30 hospitals nationwide. Thiscollaborative research model is unique and effective in acceleratingthe development of new treatments against childhood cancer.see schedule o for further program service accomplishments.in developing this collaboration, the Foundation has brought togethersome of the country's leading investigators and institutions to drivethe process of finding a cure. Investigators are performing three vitalphases of research simultaneously: basic science, translationalresearch and clinical trials. These major research components not onlyallow doctors to identify new agents in fighting Cancer, but also helpresearchers to understand the Cancer cells response to the drug.the National Pediatric Cancer Foundation is making great strides in itsmission to find a cure for childhood cancer.current initiatives of the sunshine project are as follows:sarcoma trials (osteosarcoma, rhabdomyosarcoma, ewing sarcoma,non-rhabdomyosarcoma)1. Phase ii study of nab-paclitaxel in combination with gemcitabine fortreatment of recurrent/refractory sarcoma in teenagers and young adultsthis trial will look at this combination of nab-paclitaxel andgemcitabine in its ability to prevent the formation or growth of tumorsin teenagers and young adults with relapsed or refractory osteosarcoma,ewing sarcoma, rhabdomyosarcoma and other soft tissue sarcoma. Thetrial will also look at the length of time during and after treatmentthat the disease does not get worse, and determine if nab-paclitaxelcombined with gemcitabine is safe and tolerable.2. A phase ib/ii study to evaluate the safety, feasibility and efficacyof nivolumab or nivolumab in combination with azacitidine in patientswith recurrent, resectable osteosarcoma - this will be the first timeboth drugs, nivolumab and azacitidine are being used in combination totreat osteosarcoma3. Evolutionary inspired therapy for newly diagnosed, metastatic,fusion positive rhabdomyosarcoma metastatic, fusion positive rhabdomyosarcoma (rms) have a poor outcome which is worsened with additional risk factors commonly called theoberlin criteria. Patients that meet all 4 oberlin criteria have anevent free survival (efs) of less than 20% at 2 years. All therapeuticarms on this study are designed to meet the same primary aim ofimproving the 3 year event free survival from 6% to 35% for thesepatients.4. Phase 1 trial of the lsd1 inhibitor sp-2577 in patients withrelapsed or refractory ewing sarcoma)this trial is a targeted treatment for individuals diagnosed withrefractory or recurrent ewing sarcoma, an aggressive, small round bluecell tumor typically presenting as a primary bone tumor in children andyoung adults.5. Tinks: a multi-institution study of tgf imprinted, ex vivo expandeduniversal donor nk cell infusions as adoptive immunotherapy incombination with gemcitabine and docetaxel in patients with relapsed orrefractory Pediatric bone and soft tissue sarcomas (in development) -to determine the safety of the addition of adoptive transfer ofuniversal donor, tgf imprinted (tgfi), expanded nk cells togemcitabine/docetaxel (gem/dox) for treatment of relapsed andrefractory sarcomas.brain tumor trial1. Action : adoptive cellular therapy following dose-intensifiedtemozolomide in newly-diagnosed Pediatric high-grade gliomas - animmunotherapy trial for the treatment of high grade gliomas (hgg) inchildren.2. Evaluation of digoxin for relapsed non-wnt, non-shh medulloblastoma(in development) this trial will evaluate the efficacy of digoxin intreating patients with relapsed non-shh, non-wnt medulloblastoma.non treatment trials.1. Role of myeloid-derived suppressor cells (mdsc) in the developmentof immune tolerance after allogenic hematopoietic cell transplantation(allohct) -this is an observational trial with goal of betterunderstanding the process of developing immune tolerance after bloodand marrow transplantation (bmt).2. Blood based biomarkers for minimal residual disease detection inpediatric sarcomas - the purpose of this study is to see if detectingcell-free plasma tumor dna (ptdna) and circulating tumor cells (ctc)can predict recurrence of disease in patients who are in radiographicremission 2-3 weeks after treatment. Plasma tumor dna (ptdna) is freefloating dna from the tumor found in the blood stream and circulatingtumor cells.3. Pediatric total Cancer care- this trial focuses on tissue and bloodcollection to further personalized medicine for children with cancertissue sample studies.1. Comprehensive molecular profiling of rare Pediatric and aya cancers- development of an infrastructure, methods, and standard operatingprocedure to collect and procure histology specific(esthesioneuroblastom and embryonal sarcoma) tissue resources availablethroughout the sunshine project and associated repositories.chart review study.1. Comprehensive genetic profiling for Pediatric malignanciesongoing pre-clinical trials.1. Assessment of expanded tumor infiltrating nk-cells collaborative.2. Development of personalized rna loaded nanoparticles.3. Fusion proteins by immunotherapy.sunshine project laboratorythe sunshine lab continues with the important task of finding promisingnew treatment regimens for sarcomas, among the most deadly pediatriccancer.during this past year, the sunshine lab has built on combination drugscreening platform and focused on osteosarcoma and ewing sarcoma.pediatric sarcomas often shrink or go away with initial therapy butthen later relapse and are then much more difficult to cure. Thissuggests that a small amount of disease eludes current therapy.we consider this small, resistant population should be the focus ofpreclinical research and have 3 major projects resulting from thatunderstanding of Pediatric sarcoma. 1. We have developed a model of these two competing populations,termed heterogeneity, to figure out the best strategy to eliminate bothcancer cell populations with timing and combinations of therapies. 2. In collaboration, we are investigating "second strikes" in bothosteosarcoma and ewing sarcoma. Second strikes are therapies after thedisease has shrunk with initial therapy. Rather than shrink the tumor,we are investigating therapies to eliminate the residual cells betterthan continuing the initial therapy (first strike). This resulted fromthe sunshine lab participating in the 9th annual integratedmathematical oncology workshop at moffitt Cancer center. 3. In collaboration, we have focused on a new, non-mutated target inosteosarcoma, the cmg helicase. We have both identified this as aweakness in Cancer cells more than normal cells and identified a drugclass that holds promise as an eventual therapy. We are exploring thisagent alone and in combination to maximize the chance for a successfulclinical trial. 4. In collaboration, we are building on prior publications showactivity of epigenetic drugs like panobinostat and exploring mechanismsto enhance this therapy in osteosarcoma. 5. In collaboration, we are investigating an underappreciated dnarepair enzyme as an achilles heel in ewing sarcoma called parp16.